Authors: Jerome Groopman
"I tell my patients that the more aggressive the disease, the more aggressive the treatment," Nimer said. And because it is a "bad disease," the doctor should increase his efforts rather than retreat. Sometimes even very bad diseases can be cured.
George Franklin was a successful independent investor with a cavernous apartment on Park Avenue and a weekend house in the Hudson River Valley. He had traveled to remote corners of the world, hunting and fishing and enjoying the richness of nature. I was a friend of his sister-in-law, and she told me he had the energetic spirit of a Theodore Roosevelt. About fifteen years ago, Franklin was languishing in a Manhattan hospital with a high fever and low blood cell counts. His internist was a man from his social set, advanced in years and, by his own admission, perplexed as to the cause of Franklin's problem. The hematologist who consulted on his case failed to make a diagnosis; she thought he might have aplastic anemia, a disorder where the marrow blood cells are scant. I prevailed upon George Franklin to see a specialist I knew at Memorial Sloan-Kettering, and in short order the correct diagnosis was made: T-cell lymphoma.
Lymphoma is a cancer of the lymphocytes, a type of blood cell. There are two major types of lymphocytes: B and T. Most lymphomas originate in the B cells. A smaller fraction affect T cells and are notoriously aggressive. T-cell lymphomas are, in the parlance of the corridor, bad diseases.
George Franklin was initially treated using a combination chemotherapy regimen called
ICE
, for ifosfamide, carboplatin, and etoposide. It is a difficult treatment. Franklin suffered the expected complications: mouth blisters and diarrhea. He stoically allowed that he didn't like the treatment, but he was even more unhappy when informed that it had hardly made a dent in his disease. He wanted another approach and another doctor. I suggested Stephen Nimer.
Some hematologists would have given Franklin more cycles of
ICE
, hoping that the cumulative effect would send the T-cell lymphoma into remission. But Nimer believed that the lack of any improvement, despite full doses of the regimen, demanded an immediate and radical change in therapy.
Nimer outlined a strategy with Franklin. They would try different drugs in the hope that one or more would reduce the amount of lymphoma in his body to the point where he could undergo a bone marrow transplant. Because Franklin did not have a matched donor, Nimer would harvest the stem cells from Franklin's own bone marrow, treat him with what would be lethal amounts of chemotherapy, and then "rescue" him with his own stem cells. "It scares me," Franklin said to Nimer, "but I really don't have a choice, do I?" Nimer replied that everyone always has a choice, but that this was the most rational way to proceed, and the only chance of a cure.
The way a physician phrases his recommendations can powerfully sway a patient's choices. For example, by phrasing results in the positive, patients are more likely to accept the recommendation. "We have a thirty percent chance of improvement with this approach" triggers a different reaction than "There is a seventy percent chance of failure and death," although the two statements are clinically equivalent. Also, some patients may interpret the word "improvement" to mean "cure," when in fact it can indicate only a temporary shrinkage of a cancer.
Patients also respond differently when data are presented in percentages rather than absolute numbers. For example, an elderly man in my community called to ask my opinion about treatment for a recently diagnosed colon cancer. The cancer was relatively limited and hadn't spread to any vital organs. He had multiple medical problems, and had recently undergone cardiac bypass surgery as well as a hip replacement. He was acutely aware of the quality of his life and worried more about debility from chemotherapy. One oncologist had told him that there was a 30 percent reduction in mortality if he took the chemotherapy. This sounded impressive to him, but I explained that his prognosis overall was very good, so that in five years, a 30 percent reduction in mortality might mean that out of a hundred people, ten who did not take chemotherapy would die, while seven, or 30 percent fewer, who took the chemotherapy would die. Presenting the data this way, in absolute numbers—seven versus ten out of a hundred after five years—made it clear to him which course to take: no chemotherapy.
Nimer treated George Franklin with high doses of cyclophosphamide. The T-cell lymphoma in his lymph nodes, spleen, and bone marrow melted away. Once the cancer was in remission, Nimer proceeded with bone marrow transplantation of Franklin's own stem cells. The disease disappeared for six years. During this time, Franklin continued his extensive travels, undertook some new business deals in Africa and Asia, and drew closer to his children. Then one day, drying himself off after a long swim, Franklin noticed a lump under his left armpit. The T-cell lymphoma had returned, but an extensive evaluation showed that it was confined to this area of his body. "There is no protocol, no road map about what to do at this point," Nimer explained. Of the scores of patients with Franklin's type of lymphoma who had not responded to
ICE
treatment, he was the only one who had survived more than a year. "Each person's biology is different, both the biology of his tumor and his own innate biology," Nimer told Franklin. Nimer recommended radiation to the mass under his arm, followed by a short course of chemotherapy. The disease would probably return, he allowed, but this was the least toxic form of treatment, would eradicate the local recurrence, and, he hoped, remove a tumor that could seed other parts of Franklin's body. And indeed that was the result. It was nearly two years before the lymphoma returned, this time in the marrow. "I have so much to live for," Franklin told Nimer. "Keep me alive."
At moments like this, a patient grabs hold of a doctor's heart and twists it with his plea. "I try to respect a person's wishes as best I can," Nimer later told me. Given the severity of Franklin's situation and his desperate desire to live, Nimer recommended a second bone marrow transplant. Some doctors might argue that this was too extreme, the likelihood of success too remote, the chance of failure overwhelming. All of that is true, except that without risking failure there was zero chance of success.
Franklin's second transplant was much more difficult than the first, and he was in and out of Memorial Hospital with infections over several months. But eventually he recovered, and for nearly a year returned to his normal activities. Then the cancer seemed to explode in his body, growing in large masses in his abdomen. "I am not ready to die, Jerry," Franklin told me in a quavering voice. "And I think I am going to die. I don't want to die."
It took nearly a month for Stephen Nimer to bring George Franklin to accept that everything that was humanly possible had been done, and now their joint effort should be devoted to giving him as much time as remained to be with his family and friends in comfort. "Just because you can't treat someone any longer for his cancer doesn't mean that you stop treating him," Nimer told me. In fact, it is at this stage that treatment can be most challenging: how to balance therapy with medications to control pain without so narcotizing a person that he is unaware of his surroundings and unable to communicate with loved ones; how to give words of comfort while speaking the truth, acknowledging that while the end is approaching, the person can still make a difference in the lives of others.
Many of the patients Nimer cares for face very small odds of remission and an even more remote chance of a cure. For example, he consults on the cases of many elderly people with acute leukemia, who usually fare poorly. "The question is always whether to treat or not," Nimer told me, "and I usually favor treatment." He elaborated: "What I tell people, and what I believe, is that if you don't treat a person with acute leukemia, his white blood cell count goes down and he becomes infected, or his platelet count falls and he hemorrhages. If you don't treat, then there is no chance at all that the person can get better. He will be in the hospital anyway, so in my opinion it's worth giving it a try. If you do treat them, then after chemotherapy they have low white blood cell counts, and are prone to infection, and low platelets, and prone to bleeding. But at least if you treat, then after a few weeks there is a chance they could get better and leave the hospital. If it works, then the person can have a nice year or more when he feels good. Even if it's fifteen percent, or in better cases twenty-five percent. And if it doesn't work, if the chemotherapy has no impact against the leukemia, then we can stop."
Nimer uses more than numbers to explain his advice. He cited another issue: patients and their families frequently become preoccupied with side effects when they are reluctant to undergo treatment. Oncologists have made considerable progress recently using antiemetics to control nausea and vomiting, so patients now generally do not suffer these side effects. That, in his mind, removes much of the toxicity that people might associate with chemotherapy. Nimer believes that doctors also overestimate side effects. He illustrated this point not with a dire disease like leukemia but with osteoporosis. A family member of his, a woman in her seventies, whose bone density was at the lower limit of normal and who faced a high risk of getting fractures, had consulted an internist about treatment. The physician did not want to prescribe a bisphosphonate because of recent reports, featured on the front pages of newspapers, that the drug causes the jawbone to break down. Instead, he advised a vitamin D supplement, although she had a normal diet and good intake of both this vitamin and calcium. Nimer discussed the doctor's recommendations with the family member, and favored a bisphosphonate. To validate his thinking, since bone metabolism is not his area, he spoke with Dr. John Bilezikian, a world expert in the field at New York–Presbyterian Hospital. When the family member returned to her internist, the doctor said, "But you can get jaw problems. I told you, some people who received the drug have had breakdown of the bone in the jaw."
"This frightened the woman," Nimer recounted. "I told her that is a very low risk, maybe a percent, and usually after dental work. It is something to worry about in the far future. The urgent problem was to stabilize her bones and prevent a fracture from osteoporosis. She had been focused on a side effect by her doctor, and I understand why people do focus on side effects. But that distorts the risk-to-benefit ratio." The same, he said, holds true for chemotherapy. People worry a great deal about the risks of chemotherapy, but those risks, he asserts, are minor in comparison to the potential benefits against an aggressive malignancy. "You have to deal with the problem at hand," he tells his patients.
"Most of the patients I have encountered who refused treatment do so because they are so focused on the downside," Nimer elaborated. "They are only thinking about what's happening to them that day." This is an acute insight into certain patients' psychology, and also into the psychology of certain physicians. Nimer wants his patients to adopt a broad perspective, the long view, not a vision narrowed by fear. The real concern should be the underlying disease, but that is often displaced in the patient's mind by fear of the treatment. "If you have multiple myeloma, and I suggest thalidomide, and you say you are worried about nerve damage, I reply, 'Okay, if it occurs, then we'll stop the drug. But we need to combat the cancer.'"
Paradoxically, people are more likely to worry about the well-defined side effects of a therapy than about the uncertain and seemingly boundless suffering from an illness. All of us, as James Lock, the cardiologist at Children's Hospital, pointed out earlier, instinctively latch on to certainty when faced with uncertainty. "People come to me and say, 'Dr. Nimer, I've read all about this chemotherapy, and I don't think I could ever tolerate it.' And I say, 'Maybe, but maybe you
will
tolerate it. So try it. And if it turns out you can't tolerate it, then we'll stop it.'" He continues, "If you do tolerate it, then we will continue it so long as it is tolerable, and so long as it's working." This approach, he says, "takes care of most of the ethics of decision-making."
"It's a huge responsibility," Nimer said of the ability to guide a patient and family to make a certain treatment choice. "But you begin by finding out what the patient wants, and in order to do that, you have to know how to talk to the patient." Nimer said his role is actually to help the patient figure out what he really wants and then to use the power of persuasion to show the patient the way there. Dr. Karen Delgado agreed. "This is what it really means for a person to be empowered when he is sick," she said.
Most patients don't know what they really want when confronted with a crushing diagnosis and a confusing array of treatments. "You have to show them a path that doesn't violate any principles of their life or their obligations to their family," Nimer said. "Then you help them make decisions that are medically correct and have them feel good about the decisions."
Nimer is acutely aware of how he talks with a patient, how he tries to draw out from the person the principles of his life and his family obligations. This kind of information cannot be captured in an algorithm, nor is it to be found in the alphabet soup of chemotherapy acronyms or in a quantified classification scheme. It transcends statistics and the latest research paper in the medical literature. As Nimer put it, "Their choice has to be consistent with their philosophy of living."
He reminded me of a patient we both cared for years ago who asserted that quality of life had no significance to him; only life itself mattered, however painful or difficult staying alive might be. He would not recoil from the most debilitating chemotherapy and radiation treatments. He had only one goal, he said: to be cured. Another patient we also shared in care with the same type of blood cancer ultimately decided that the cost was too great, the odds too long, and the suffering too extreme. He chose not to continue his treatment. In each case, Nimer worked with the patient to find the choice that made sense to him. While their diseases were biologically similar, their philosophies of life diverged.